Mitochondrial DNA Disorders

Question 1

What is the respiratory chain, in reference to mitochondria?

Answer 1

A series of 5 membrane-bound protein complexes collectively responsible for oxidative phosphorylation.

Question 2

Are most mitochondrial genes encoded by nuclear or mitochondrial DNA?

Answer 2

Nuclear.

Question 3

What is the diameter of mitochondria?

Answer 3

1 micrometer.

Question 4

What is the size of one mitochondrial chromosome?

Answer 4

16.6 kb

Question 5

How many DNA molecules are there per mitochondria?

Answer 5

2-10

Question 6

What percentage of mitochondria DNA is GC?

Answer 6

44%

Question 7

What nucleotide is the heavy strand of mitochondria rich in?

Answer 7

Guanine

Question 8

What nucleotide is the light strand of mitochondria rich in?

Answer 8

Cytosine

Question 9

What is the D loop in mitochondrial DNA?

Answer 9

Small section of triple-stranded DNA due to repeat synthesis of a short segment of the H stand DNA. It is a regulatory region and contain hypervariable regions.

Question 10

How many genes are the on a mitochondrial chromosome?

Answer 10

37

Question 11

How many mitochondrial genes specify RNA products?

Answer 11

24

Question 12

How many mitochondrial genes encode proteins?

Answer 12

13

Question 13

What percentage of mitochondrial DNA is coding?

Answer 13

93%

Question 14

What percentage of mitochondrial DNA is non-coding?

Answer 14

7%

Question 15

What region of mitochondrial DNA is non-coding?

Answer 15

D-loop

Question 16

Does mitochondrial DN contain introns?

Answer 16

No

Question 17

Describe the positioning of mitochondrial genes in relation to each other.

Answer 17

Continuous, separated by 1-2 non-coding bases or overlapping.

Question 18

Explain how the bottleneck effect affects inheritance of mitochondrial genes.

Answer 18

If the mother has heteroplasmy, her primordial germ cells will all contain different mitochondria. As they contain very few mitochondria they will have different numbers of different mitochondria.

Question 19

What are the four reasons for higher functional mutation rates in mitochondrial compared to nuclear DNA?

Answer 19

93% is coding- higher chance of functional mutation
More rounds of replication- more chance for errors
No histone protection of DNA- oxidative damage (+ mitochondrial function)
Lack of adequate repair mechanisms.

Question 20

How can heteroplasmy in an individual hinder diagnosis of a mitochondrial disease?

Answer 20

Heteroplasmy may be tissue specific. E.g. analysing blood will not diagnose affected muscle.

Question 21

Can nuclear DNA cause of modify the mitochondrial genotype?

Answer 21

Yes

Question 22

What are some symptoms of mitochondrial disease?

Answer 22

Neurological signs, encephalopathy, dementia, ataxia, dystonia, neuropathy, seizures, myopathy, hypotonia, weakness, cardiomyopathy. Also deafness, diabetes, retinal pigmentation, acidosis.

Question 23

Do all mitochondrial diseases follow an all-or-nothing principle?

Answer 23

No, some are of quantitative measure and appear at a threshold.

Question 24

What mitochondrial mutations cause leber hereditary optic neuropathy (LHON)?

Answer 24

NADH dehydrogenase subunits 1, 2, 6 (ND1, ND24, ND6) and m11778G-A.

Question 25

A mutation in what mitochondrial gene causes NARP/ Leigh syndrome?

Answer 25

Subunit 6 of ATPase (m1624C-T).

Question 26

Give examples of two homoplasmic mitochondrial disorders?

Answer 26

Leber hereditary optic neuropathy (LHON) and NARP/Leigh syndrome.

Question 27

Give two examples of heteroplasmic mitochondrial diseases.

Answer 27

MELAS and MERFF.

Question 28

What mitochondrial mutation causes MELAS?

Answer 28

Mutation in leucine in tRNA (m3243A-G).

Question 29

What mitochondrial mutation causes MERFF?

Answer 29

Mutation in lysine in tRNA (m8344G-A; m8356T-C).

Question 30

Why does mitochondrial DNA's high mutation rate benefit forensics and evolutionary studies.

Answer 30

Easy to efficiently assay diversity in many samples. | Polymorphisms are easier to find than in nuclear DNA.

Question 31

Compare the mutation rate in mitochondrial DNA to nuclear DNA.

Answer 31

50-100 times higher

Question 32

What regions of mitochondrial DNA are particularly useful for forensic and evolutionary studies?

Answer 32

HV1 and HV2.

Question 33

What are the advantages of HV1 and HV2?

Answer 33

High variety, small (250-350bp) so easy to amplify using PCR.

Question 34

How is an individual's mitochondrial DNA sequence interpreted?

Answer 34

It is compared to the standard reference sequence (Cambridge/Oxford). Relative's mtDNA can then be compared.

Question 35

What is a major advantage of mitochondrial DNA over nuclear DNA in forensic and evolutionary studies.

Answer 35

Its high quantity.